Genetic Variant POLR2C:c.387+125C>T (chr16-57469418-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_032940.3(POLR2C):c.387+125C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000108 in 924,982 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000011 ( 0 hom. )

Consequence

POLR2C
NM_032940.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.218

Publications

0 publications found

Variant links:

Genes affected

POLR2C (HGNC:9189): (RNA polymerase II subunit C) This gene encodes the third largest subunit of RNA polymerase II, the polymerase responsible for synthesizing messenger RNA in eukaryotes. The product of this gene contains a cysteine rich region and exists as a heterodimer with another polymerase subunit, POLR2J. These two subunits form a core subassembly unit of the polymerase. A pseudogene has been identified on chromosome 21. [provided by RefSeq, Jul 2008]

POLR2C links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLR2C	NM_032940.3 link	c.387+125C>T		intron_variant	Intron 5 of 8	ENST00000219252.10	NP_116558.1	P19387Q6FGR6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLR2C	ENST00000219252.10 link	c.387+125C>T		intron_variant	Intron 5 of 8	1	NM_032940.3	ENSP00000219252.4		P19387

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000108

AC:

AN:

924982

Hom.:

Cov.:

AF XY:

0.00000209

AC XY:

AN XY:

478612

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23162

American (AMR)

AF:

0.00

AC:

AN:

38136

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21956

East Asian (EAS)

AF:

0.00

AC:

AN:

35602

South Asian (SAS)

AF:

0.00

AC:

AN:

72254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46718

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4772

European-Non Finnish (NFE)

AF:

0.00000156

AC:

AN:

639744

Other (OTH)

AF:

0.00

AC:

AN:

42638

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

(source)

DANN

Benign

0.69

PhyloP100

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over